Intravenous Trastuzumab Research Articles

Cost-minimisation analysis of intravenous versus subcutaneous trastuzumab regimen for breast cancer management in Hong Kong.

In 2017, breast cancer was the most common cancer and third leading cause of cancer death among women in Hong Kong. Approximately 20% of patients were human epidermal growth factor receptor-2 (HER2)-positive. This study was conducted to investigate cost differences between intravenous and subcutaneous trastuzumab regimens in Hong Kong using medical resources utilisation data from other countries. A cost-minimisation model was developed to compare the cost of total care, including direct medical cost and full-time equivalent (FTE) hours. The drug acquisition cost was obtained from the manufacturer, whereas the costs for hospitalisation and clinic visits were acquired from the Hong Kong Gazette. Time (in FTE hours) was determined by literature review. All costs were expressed in US dollars (US$1 = HK$7.8). Costs were not discounted because of the short time horizon. One-way deterministic sensitivity analysis was performed to identify the effects of changes in drug acquisition cost, changes in FTE hours (based on confidence intervals reported), and changes in body weight (±20%). Literature review indicated that 0.18 FTE hour of nursing time (7.9 hours) and 0.14 FTE hour of pharmacist time (6.2 hours) could be saved each week if the subcutaneous formulation was used. Using data in 2017, after 18 cycles of treatment with subcutaneous trastuzumab, the drug acquisition and healthcare professional time costs were reduced by US$9451.28 and US$566.16, respectively, yielding an annual savings of over US$8 million. The subcutaneous formulation of trastuzumab is a potential cost-saving therapy for HER2-positive breast cancer patients in Hong Kong. The drug acquisition cost was the parameter with the greatest effect on the total cost of treatment.

Neoadjuvant pyrotinib, trastuzumab, and docetaxel for HER2-positive breast cancer (PHEDRA): a double-blind, randomized phase 3 trial

BackgroundPyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine has survival benefits and acceptable tolerability in patients with HER2-positive metastatic breast cancer. We further assessed addition of pyrotinib to trastuzumab and docetaxel in the neoadjuvant setting.MethodsIn this multicenter, double-blind, phase 3 study (PHEDRA), treatment-naive women with HER2-positive early or locally advanced breast cancer were randomly assigned (1:1) to receive four neoadjuvant cycles of oral pyrotinib or placebo (400 mg) once daily, plus intravenous trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg) and docetaxel (100 mg/m2) every 3 weeks. The primary endpoint was the total pathological complete response (tpCR; ypT0/is and ypN0) rate per independent central review.ResultsBetween Jul 23, 2018, and Jan 8, 2021, 355 patients were randomly assigned, 178 to the pyrotinib group and 177 to the placebo group. The majority of patients completed four cycles of neoadjuvant treatment as planned (92.7% and 97.7% in the pyrotinib and placebo groups, respectively). The tpCR rate was 41.0% (95% CI 34.0 to 48.4) in the pyrotinib group compared with 22.0% (95% CI 16.6 to 28.7) in the placebo group (difference, 19.0% [95% CI 9.5 to 28.4]; one-sided P < 0.0001). The objective response rate per investigator was 91.6% (95% CI 86.6 to 94.8) in the pyrotinib group and 81.9% (95% CI 75.6 to 86.9) in the placebo group after the neoadjuvant treatment, resulting in an increase of 9.7% (95% CI 2.7 to 16.6). The most common grade 3 or worse adverse events were diarrhea (79 [44.4%] in the pyrotinib group and nine [5.1%] in the placebo group), neutropenia (33 [18.5%] and 36 [20.3%]), and decreased white blood cell count (29 [16.3%] and 24 [13.6%]). No deaths were reported during neoadjuvant treatment.ConclusionsThe primary endpoint of the study was met. Neoadjuvant pyrotinib, trastuzumab, and docetaxel significantly improved the tpCR rate compared with placebo, trastuzumab, and docetaxel, with manageable toxicity, providing a new option for HER2-positive early or locally advanced breast cancer.Trial registrationClinicalTrials.gov, NCT03588091

Incidence and severity of anaphylaxis and hypersensitivity in trials of intravenous pertuzumab plus trastuzumab or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection for HER2-positive breast cancer

AimTo characterise risk of anaphylaxis/hypersensitivity with intravenous pertuzumab plus trastuzumab (PH IV), the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) or concomitant chemotherapy to support potential administration of PH FDC SC by healthcare professionals outside clinics. MethodsA cumulative search for anaphylaxis/hypersensitivity (Roche Standard Adverse Event Group Terms) was performed for all pivotal trials cited in the current EMA P IV/PH FDC SC summaries of product characteristics: MBC: NCT00567190, NCT02402712; EBC: NCT01358877, NCT00545688, NCT00976989, NCT02132949, NCT03493854 and NCT03674112. Occurrence, incidence and severity of events were analysed and a time–trend analysis (by cycle) was performed. ResultsThis analysis includes 4772 patients who received PH IV and/or PH FDC SC. Incidence of all-grade (grade ≥3) anaphylaxis/hypersensitivity events: 3–11% (≤2%) for PH IV MBC trials; 1–13% (0–3%) for PH IV EBC trials; and 2–3% (<1%; not related to PH FDC SC) for PH FDC SC EBC trials. Discontinuations due to anaphylaxis/hypersensitivity were rare for PH IV (generally <1% except two arms of TRYPHAENA: 1% and 3%); no discontinuations of PH FDC SC have been recorded so far. Time–trend analysis showed that most events were reported during the first 6–8 cycles with concurrent chemotherapy, with a decrease in later cycles (except MetaPHER). ConclusionPH IV and PH FDC SC were well tolerated, with few grade ≥3 anaphylaxis/hypersensitivity events reported with PH IV and no grade ≥3 related events with PH FDC SC. Most events occurred during chemotherapy.

Comparison Adverse Events on Intravenous Versus Subcutaneous Trastuzumab as Part of Adjuvant Therapy for Breast Cancer

Comparison Adverse Events on Intravenous Versus Subcutaneous Trastuzumab as Part of Adjuvant Therapy for Breast Cancer

Trastuzumab and pertuzumab combination therapy for advanced pre-treated HER2 exon 20-mutated non-small cell lung cancer

IntroductionIn 1–3% of non-small cell lung cancer (NSCLC) human epidermal growth factor 2 (HER2) mutations are identified as a genomic driver. Nevertheless, no HER2-targeted treatment is approved for NSCLC. In the Drug Rediscovery Protocol (DRUP), patients are treated with off-label drugs based on their molecular profile. Here, we present the results of the cohort ‘trastuzumab/pertuzumab for HER2 exon20 mutation positive (HER2m+) NSCLC’. MethodsPatients with treatment refractory, advanced HER2m+ NSCLC with measurable disease (RECISTv1.1) were eligible. Treatment with intravenous trastuzumab combined with pertuzumab every 3 weeks was administered. The primary end-point was clinical benefit (CB: either objective response or stable disease ≥ 16 weeks). Patients were enrolled using a Simon-like 2-stage design, with 8 patients in stage 1 and up to 24 patients in stage 2 if at least 1 patient had CB in stage 1. At baseline, a biopsy for biomarker analysis, including whole genome sequencing, was obtained. ResultsTwenty-four evaluable patients were enrolled and treated between May 2017 and August 2020. CB was observed in 9 patients (38%); including an objective response rate of 8.3% (2 patients had a partial response) and 7 patients with stable disease ≥ 16 weeks. The most frequently observed HER2 mutation was p.Y772_A775dup (71%, n = 20). Median follow-up was 13 months, median progression-free survival and overall survival 4 (95% CI 3–6) and 10 months (95% CI 4 – not reached), respectively. Whole genome sequencing data (available for 67% of patients) confirmed the inclusion mutation in all cases. No unexpected toxicity was observed. ConclusionDespite the fact that the study did meet its primary end-point, trastuzumab/pertuzumab was only marginally active in a subset of patients with heavily pre-treated HER2m+ NSCLC.

Primary results from JUPITER, a phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with HER2-amplified solid tumors.

3131 Background: Human epidermal growth factor receptor 2 (HER2) gene amplification or mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric cancers, but also in a variety of cancers. Despite its considerable therapeutic potential, the evidence has not been established. To address this unmet need, we conducted an organ-agnostic basket trial targeting HER2-amplified solid tumors. Methods: JUPITER is a multicenter, single-arm, phase 2 basket trial for solid tumor patients (pts) with HER2 amplification determined by next-generation sequencing (NGS). Both tissue and liquid NGS results were allowed. HER2 amplification by ISH or HER2 overexpression by IHC were not used for inclusion. Pts had treatment-refractory metastatic tumors, or rare cancers without established standard of care. Breast, gastric, and colorectal cancers were excluded. Pts were treated with intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks until disease progression or any other reason for discontinuation. Tumor response was assessed using RECIST v1.1. Primary endpoint was ORR by blinded independent central review (BICR), and secondary endpoints were ORR assessed by the investigators, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. We set the ORR threshold 5% and expected ORR was 20%. Estimated sample size was 38 patients with one-sided alpha 2.5% and power 80%. Results: Between April 2019 and June 2020, 42 pts were consented, and 40 pts were treated. Median age was 62 (range, 21-86) and 60% were females. The most common diagnosis was biliary tract cancer (20%), followed by salivary ductal carcinoma (12.5%) and endometrial cancer (12.5%). At data cutoff (1 Sep 2021), ORR by BICR was 22.5% (95%CI: 10.8%-38.5%). ORR assessed by the investigator was 25% (95%CI: 12.7%-41.2%). PFS, OS and DOR were not reached at data cutoff; 3 responders remained on treatment. Of 40 pts, 32.5% had grade ≥ 3 adverse events; 10% were treatment-related, including neutropenia, hypertension, peripheral sensory neuropathy and lymphoedema (all grade 3). No treatment-related death was observed. Exploratory biomarker analysis of response and resistance is in progress. Conclusions: Combination therapy with trastuzumab and pertuzumab was well tolerated and showed promising efficacy for the patients with HER2-amplified solid tumors determined by NGS. Clinical trial information: jRCT2031180150.

White Paper on the Value of Time Savings for Patients and Healthcare Providers of Breast Cancer Therapy: The Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection as an Example.

Health technology assessments and value frameworks are becoming increasingly important for clinical decision-making. Most of these frameworks, however, focus on value to payers rather than patients and healthcare providers and may ignore other sources of economic value such as patient and physician time cost, impact on productivity, and direct health system costs. This article focusses on fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in the treatment of HER2-positive breast cancer. We review relevant clinical evidence, examine data on time and resource use of the subcutaneous administration of trastuzumab compared with intravenous treatment and how it can be extrapolated to PH FDC SC, and discuss the value PH FDC SC can bring to patients and healthcare providers. We will also provide our own experiences of PH FDC SC from the healthcare (oncologist, healthcare economist, pharmacist) and patient point of view. The data, combined with our personal experiences, suggest that switching from intravenous pertuzumab and trastuzumab to PH FDC SC could reduce non-drug costs for healthcare providers treating patients with HER2-positive breast cancer through time savings and other economic benefits. Furthermore, PH FDC SC could also save patient time given its shorter administration and post-injection observation time versus intravenous infusions, potentially resulting in reduced productivity loss. These benefits could be applied to other subcutaneous formulations, either currently available or in development.

Utilization of Intravenous (IV) Curcumin, Genistein, and Trastuzumab to Reduce HER2 receptors in Breast Cancer Patients

In recent decades, due to the increased growth, spread, and onset of cancer, interest has arisen in studying the methods that could be used to combat it. Breast cancer is the most prevalent form of cancer in the world. Due to the growing pervasiveness of this issue, a larger body of research is forming in the area of breast cancer with the intent to contain the spread of the potentially ravaging disease or diagnose it earlier. This research is intended to propose an alternative, possibly more efficient method to inhibit the chances of metastasis and continued prevalence of breast cancer in a patient. The related work discusses similar research being done and builds on it to incorporate the novel method being proposed while explaining the components of the proposed treatment in question. The proposed method aims to deplete HER2 protein receptors in breast cancer patients through the intravenous (IV) administration of the tyrosine kinase inhibitors (TKIs) curcumin and genistein, as well as trastuzumab, which is more commonly known under the brand name Herceptin. Depleting HER2 protein receptors can potentially cause the severity of HER2-positive breast cancer to decrease substantially, as well as reduce the probability of metastasis and recurrence, the rate of which is considerably higher in HER2-positive cases when compared to that of HER2-negative cases. The future work deals with alternate methods that could be explored with a similar intent as this research study and describes the potential implications of the study.

Population pharmacokinetic and exploratory exposure\u2013response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study

PurposeTo characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous pertuzumab plus trastuzumab); derive individual pertuzumab exposures in the PH FDC SC arm for subsequent pertuzumab exposure–response (ER) analyses; compare observed trastuzumab PK with predicted exposures from a previous SC trastuzumab model; assess whether pertuzumab affects trastuzumab PK; evaluate pertuzumab exposure–efficacy and –safety relationships and support the approved SC dosing regimen.MethodsPopulation pharmacokinetic modeling and simulations were used to describe the data. Standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks were used for model performance assessment. Covariates were included from previously reported models. ER analysis was conducted using logistic regression.ResultsSC pertuzumab PK was described adequately by a two-compartment model with first-order absorption; significant covariates included in the final model were albumin, lean body weight, and Asian region; however, these appeared not to be clinically relevant. Trastuzumab concentrations were described adequately by the previous model; there was no evidence of a pertuzumab effect on trastuzumab PK as part of PH FDC SC and higher model-predicted pertuzumab exposure was not associated with differences in pathologic complete response rate or an increased probability of selected grade ≥ 3 adverse events of interest.ConclusionThe approved PH FDC SC dose [loading: 1200/600 mg pertuzumab/trastuzumab (15 mL); maintenance: 600 mg pertuzumab/trastuzumab (10 mL) and 2000 U/mL recombinant human hyaluronidase every 3 weeks] provides a positive benefit–risk profile with comparable efficacy and safety to intravenous pertuzumab plus trastuzumab.

Safety and tolerability of subcutaneous trastuzumab and intravenous pertuzumab as adjuvant treatment for HER2 positive breast cancer: a pilot study

BackgroundSubcutaneous (SC) trastuzumab is similar to intravenous trastuzumab in terms of pharmacokinetics, efficacy and tolerability. The use of dual anti-HER2 agents trastuzumab and pertuzumab has become the new standard for...

Dual-targeted therapy with pyrotinib and trastuzumab for HER2-positive advanced colorectal cancer: Preliminary results from a multicenter phase 2 trial.

e15554 Background: HER2 is an emerging treatment target for colorectal cancer (CRC). Previous phase 2 trials have demonstrated the promising antitumor activity of dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab in HER2-positive metastatic CRC. Pyrotinib, a novel irreversible HER2/EGFR dual tyrosine kinase inhibitor, has been approved for breast cancer in 2018 in China. The antitumor effect of pyrotinib was also shown in other solid tumors, such as lung cancer and gastric cancer. The randomized phase 3 PHOEBE trial proved that the efficacy of pyrotinib was better than lapatinib when in combination with capecitabine in HER2-positive local relapsed or metastatic breast cancer. We reported preliminary results of pyrotinib plus trastuzumab in patients with HER2-positive advanced CRC from an ongoing multicenter phase 2 trial (NCT04380012). Methods: Patients with confirmed recurrent/metastatic CRC, HER2-positive disease, and ECOG performance status 0-2, received oral pyrotinib 400 mg once a day plus intravenous trastuzumab 8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks. The primary endpoint was objective response rate (ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. The data cutoff date was December 24, 2020. Results: From December 2019 to November 2020, a total of 11 patients were enrolled. The median age was 57 (range, 44-70) years and 73% (8/11) of patients were male. The number of prior therapy lines was 0, 1, and ≥2 in 1 (9%), 2 (18%), and 8 (73%) patients, respectively. One (9%) patient only showed HER2 overexpression, 7 (64%) showed HER2 amplification and overexpression, and 3 (27%) showed HER2 mutation and overexpression. The detection of co-mutations showed that 5 (45%) patients had KRAS mutations, 1 (9%) had NRAS mutation, and none had BRAF mutation. Three patients achieved partial response, with an ORR of 27% (3/11) in the total population, 50% (3/6) in KRAS wild-type patients, and 60% (3/5) in patients with wild type of both KRAS and NRAS, respectively. The disease control rate was 45% (5/11). The most common (occurring in at least 2 patients) grade ≥3 adverse event was diarrhea (73% [8/11]). Dose interruption owing to diarrhea occurred in 7 (64%) patients, and 5 (45%) patients reduced the dose to 320 mg due to diarrhea. No treatment-related death was observed. Conclusions: Pyrotinib combined with trastuzumab showed promising ORR with acceptable safety in patients with HER2-positive advanced CRC, suggesting a potential treatment option, especially in those without co-mutations. Clinical trial information: NCT04380012.

Simulating Costs of Intravenous Biosimilar Trastuzumab vs. Subcutaneous Reference Trastuzumab in Adjuvant HER2-Positive Breast Cancer: A Belgian Case Study.

This study aimed to compare drug costs and healthcare costs of a 1 year adjuvant course with intravenous biosimilar trastuzumab vs. subcutaneous reference trastuzumab in HER2-positive breast cancer from the Belgian hospital perspective. Our simulation is based on the methodology used by Tjalma and colleagues, and considered costs of drugs, healthcare professional time and consumables. We calculated intravenous drug costs for different body weights, and computed drug costs and healthcare costs to treat 100 patients with either trastuzumab formulation, assuming a binomial body weight distribution in this sample. Scenarios were run to account for drug discounts and intravenous vial sharing. Drug costs amounted to €1,431,282 with intravenous biosimilar trastuzumab and €1,522,809 with subcutaneous reference trastuzumab for a sample of 100 patients in the base case analysis. When healthcare professional time and consumables were also considered, healthcare costs with intravenous biosimilar trastuzumab were similar to those with subcutaneous reference trastuzumab. Differences in healthcare costs between intravenous biosimilar trastuzumab and subcutaneous reference trastuzumab depended on the level of discounts on these formulations and on intravenous vial sharing. Our case study demonstrates that comparing costs of intravenous vs. subcutaneous formulations is complex and multifactorial, and entails more than a simple cost comparison of products.

Subcutaneous trastuzumab with pertuzumab and docetaxel in HER2-positive metastatic breast cancer: Final analysis of MetaPHER, a phase IIIb single-arm safety study

PurposeIntravenous trastuzumab, pertuzumab, and docetaxel are first-line standard of care for patients with HER2-positive metastatic breast cancer (mBC). MetaPHER is the first study assessing the safety and tolerability of subcutaneous trastuzumab plus intravenous pertuzumab and chemotherapy in a global patient population with HER2-positive mBC.MethodsIn this open-label, single-arm, multicenter, phase 3b study, eligible patients were ≥ 18 years old with histologically/cytologically confirmed previously untreated HER2-positive mBC. All received ≥ 1 subcutaneous trastuzumab 600 mg fixed dose plus intravenous pertuzumab (loading dose: 840 mg/kg; maintenance: 420 mg/kg) and docetaxel (≥ 6 cycles; initial dose 75 mg/m2) every 3 weeks. The primary objective was safety and tolerability; secondary objectives included efficacy.ResultsAt clinical cutoff, 276 patients had completed the study; median duration of follow-up was 27 months. The most common any-grade adverse events were diarrhea, alopecia, and asthenia; the most common grade ≥ 3 events were neutropenia, febrile neutropenia, and hypertension. There were no cardiac deaths and mean left ventricular ejection fraction was stable over time. Median investigator-assessed progression-free survival was 18.7 months; objective response rate was 75.6%.ConclusionsSafety and efficacy with subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in mBC are consistent with historical evidence of intravenous trastuzumab with this combination. Findings further support subcutaneous administration not affecting safety/efficacy profiles of trastuzumab in HER2-positive BC with increased flexibility in patient care. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection has recently been approved for the treatment of HER2-positive early/mBC, further addressing the increasing relevance of and need for patient-centric treatment strategies.Trial registrationNCT02402712

Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer.

The antitumor efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapies, such as humanized monoclonal antibody trastuzumab (Herceptin®, Roche), in patients with breast-to-brain cancer metastasis is hindered by the low permeability of the blood-brain barrier (BBB). NEO100 is a high-purity version of the natural monoterpene perillyl alcohol, produced under current good manufacturing practice (cGMP) regulations, that was shown previously to reversibly open the BBB in rodent models. Here we investigated whether NEO100 could enable brain entry of trastuzumab to achieve greater therapeutic activity. An in vitro BBB, consisting of human astrocytes and brain endothelial cells, was used to determine trastuzumab penetration in the presence or absence of NEO100. For in vivo studies, we administered intravenous (IV) trastuzumab or the trastuzumab-drug conjugate ado-trastuzumab emtansine (T-DM1; Kadcyla®, Roche), to mouse models harboring intracranial HER2+ breast cancer, with or without BBB opening via IA NEO100. Brain and tumor tissues were examined for the presence of trastuzumab and infiltration of immune cells. Therapeutic impact was evaluated based on overall survival. NEO100 greatly increased trastuzumab penetration across an in vitro BBB. In vivo, IA NEO100-mediated BBB opening resulted in brain tumor-selective accumulation of trastuzumab, without detectable presence in normal brain tissue, along with increased presence of immune cell populations. IV delivery of trastuzumab or T-DM1 achieved significantly greater overall survival of tumor-bearing mice when combined with IA NEO100. IA NEO100 facilitates brain tumor entry of trastuzumab and T-DM1 and significantly enhances their therapeutic efficacy, along with increased antibody-dependent immune cell recruitment.

The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+\u2009and androgen receptor-positive metastatic or locally advanced breast cancer

PurposeAndrogen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab.MethodsEligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety.ResultsOverall, 103 women were enrolled [median age 60 years (range 34–83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0–3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs.ConclusionsEnzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination.ClinicalTrials.gov numberNCT02091960

Abstract PS9-68: Budget impact of Ontruzant for the treatment of breast cancer and gastric cancer in the United States

Abstract OBJECTIVES: Breast cancer is estimated to have the highest incidence among all cancers in the United States (US) in 2020. In turn, the incidence of gastric cancer is ranked fifteenth among all cancers in the US. Targeted therapies, such as trastuzumab, have drastically improved clinical outcomes for patients with over-expressive human epidermal growth factor receptor 2 (HER2+) in early-stage breast cancer (EBC) and metastatic breast cancer (MBC) as well as metastatic gastric cancer (MGC). However, due to the high cost of treatment and eligible patient population size, originator trastuzumab has caused patient affordability challenges and represents a high budget burden on payers. The objective of this study is to assess the potential financial impact associated with the use of intravenous (IV) trastuzumab biosimilar Ontruzant compared to the originator, in patients with HER2+ EBC, MBC and MGC from the US healthcare payer perspective. METHODS: A budget impact model with a 5-year time horizon was developed to compare costs ($; 2020) under scenarios with and without the entry of Ontruzant to a healthcare plan. Only direct costs were considered following a payer perspective. Drug acquisition costs were estimated based on the published wholesale acquisition cost (WAC) price. The target population consisted of incident HER2+ patients eligible to receive trastuzumab IV or subcutaneous. Epidemiological data were obtained from SEER database and Epic Oncology. Predictions on trastuzumab market share and Ontruzant uptake were based on internal market research. The model calculated the budget impact of Ontruzant by indication and across all indications. RESULTS: In a hypothetical healthcare plan with one million members, the number of incident patients treated with the trastuzumab class was estimated to range from 107 in year 1 to 100 in year 5 in HER2+ EBC and 17 to 16 in HER2+ MBC. About ten new patients with HER2+ MGC were estimated to be treated with trastuzumab or biosimilars each year in year 1 to 5. The market uptake of Ontruzant with the trastuzumab class was assumed 50% in year 1 and rising over time to 90% in year 5, which led to a total budget saving of $13,534,498 in EBC and MBC and $459,331 in MGC over the 5-year period for the healthcare plan. The model yielded an average saving of $1,859, $2,073 and $766 per treated member per month in EBC, MBC and MGC, respectively. The cost saving was mainly driven by the lower drug acquisition cost of Ontruzant compared to originator trastuzumab, as well as potential reduction of vial wastage due to the availability of Ontruzant multi-dose vials. CONCLUSIONS: Adding Ontruzant to the formulary for treatment of HER2+ breast cancer and gastric cancer and creating mechanisms to encourage providers to utilize Ontruzant instead of the reference branded agent, could lead to substantial cost-savings for the US healthcare payers; and consequently, improve access to treatments for the patients. Citation Format: Min Huang, Puneet Singhal, Reshma Shinde, Sarah K Wilkes, Nirav Nagda, Yunni Yi, Stefano Lucherini. Budget impact of Ontruzant for the treatment of breast cancer and gastric cancer in the United States [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-68.

Cost-efficiency and expanded access modeling of conversion to biosimilar trastuzumab-dkst with or without pertuzumab in metastatic breast cancer

Aims To investigate the cost-efficiency and budget-neutral expanded access of biosimilar intravenous trastuzumab-dkst versus reference intravenous (trastuzumab-IV) and subcutaneous trastuzumab (trastuzumab-SC) (with/without pertuzumab) in metastatic breast cancer (MBC). Methods Economic simulation modeling in a panel of 1,000 MBC patients to estimate: 1) cost-savings by conversion from trastuzumab-IV or trastuzumab-SC to trastuzumab-dkst at 10-100% conversion rates in 3 weight groups: first quartile (Q1:62.2 kg), median (73.1 kg), third quartile (Q3:88.6 kg), and 2) budget-neutral expanded access to trastuzumab-dkst from cost-savings. Results In monotherapy, conversion (%) from trastuzumab-IV generates one-year cost-savings from $2,272,189 (Q1;10%) to $31,506,804 (Q3;100%) and from trastuzumab-SC monotherapy savings range from $2,071,277 (Q3;10%) to $35,775,475 (Q1;100%). In combination with pertuzumab, trastuzumab-dkst is cost-efficient in all patient weights with one-year savings over trastuzumab-IV up to $32,662,714 (Q3;100%) and over trastuzumab-SC up to $35,322,461 (Q1;100%). Savings from conversion from trastuzumab-IV monotherapy could provide between 3,087 (Q1;10%) and 30,911 (Q3;100%) additional trastuzumab-dkst doses—enough to treat 58 to 583 patients for one year. Conversion from trastuzumab-SC monotherapy could provide between 1,559 (Q3;10%) and 48,598 (Q1;100%) additional trastuzumab-dkst doses or 38 to 918 additional one-year treatments with trastuzumab-dkst. In combination with pertuzumab, conversion from trastuzumab-IV could provide from 311 (Q1;10%) to 3,939 (Q3;100%) maintenance doses (pertuzumab + trastuzumab-dkst) or 17 to 210 additional one-year regimens (all agents). Savings from conversion from trastuzumab-SC could expand access to 226 (Q3;10%) to 4,782 (Q1;100%) additional maintenance doses or 12 to 254 one-year regimens. Conclusions This first cost-efficiency and expanded access study of biosimilar therapeutic cancer agents shows that trastuzumab-dkst is cost-efficient over trastuzumab-IV and trastuzumab-SC across all patient weights in both monotherapy and combination with pertuzumab and paclitaxel. These cost savings could provide more patients with trastuzumab-dkst treatment on a budget-neutral basis.

Budget Impact Analysis of the Introduction of Rituximab and Trastuzumab Intravenous Biosimilars to EU-5 Markets.

BackgroundBiologic treatments impose a large financial burden on healthcare payers. Subcutaneous formulations of trastuzumab and rituximab offer administration cost savings relative to the intravenous products through reduced preparation and infusion times. However, intravenous biosimilars have the potential to offset administration costs through lower drug costs.ObjectiveThe objective was to develop a budget impact model (BIM) from a payer’s perspective for the EU-5 countries (UK, France, Germany, Spain, Italy) to demonstrate the economic impact of using intravenous trastuzumab and rituximab biosimilars.MethodsAn incidence-based BIM was developed to estimate the net budget impact utilising epidemiology data from the literature, market research data on the use of relevant treatments in all approved indications, and corresponding costs. The budget impact was estimated for 5 years following introduction of the biosimilars.ResultsAnalysis using the base-case results indicated that adoption of the biosimilars trastuzumab and rituximab would result in net cost savings. At year 5, the net budget saving ranged from €4.05 million to 303.86 million for rituximab and from €19 million to 172 million for trastuzumab. The cost saving could potentially extend treatment to 291–15,671 more patients with rituximab and 622–3688 more patients with trastuzumab.ConclusionThis budget impact analysis emphasised that increased use of intravenous rituximab and trastuzumab biosimilars may result in cost savings from the payer’s perspective across the EU-5 countries.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40259-020-00461-8.

Budget impact analysis of subcutaneous trastuzumab compared to intravenous trastuzumab in Saudi HER2-positive breast cancer patients

ABSTRACT Background: This study was aimed to assess the budget impact of SC trastuzumab compared to IV trastuzumab in patients with HER2-positive breast cancer (BC) from the perspective of the governmental health sector in Saudi Arabia, over a 3-year time horizon. Methods: A model was developed to calculate the direct medical and indirect costs for 394 incidents HER2-positive BC patients per year who would receive SC trastuzumab compared to IV formulation. We calculated drug acquisition costs for fixed, loading, and subsequent doses of trastuzumab. One-way sensitivity analysis was conducted. Results: Two scenarios were modeled: the first scenario evaluated the impact of gradual replacement of IV formulation by SC, the second scenario, evaluated impact of totally replacing IV formulation. The total annual costs in the first scenario were estimated to be SAR 177 million (USD 98 million) for IV trastuzumab compared to SAR 143 million (USD 79 million) for SC formulation, leading to a total budget saving of SAR 34,527,346 (USD 19,181,858). In the second scenario, the total annual costs were estimated to be SAR 108 million (USD 60 million) for SC trastuzumab compared to SAR 177 million (USD 98 million) for IV formulation, leading to budget savings of SAR 69,054,692 (USD 36,363,717). Conclusion: Benefits of the SC formulation over IV infusions are being converted to realistic monetary benefits for all providers and payers.

FDA Approval Summary: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf Injection for Subcutaneous Use in Patients with HER2-positive Breast Cancer.

On June 29, 2020, the FDA approved pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (Phesgo) for the treatment of patients with HER2-positive early-stage and metastatic breast cancer. Patients should be selected for therapy based on an FDA-approved companion diagnostic test. Approval was primarily based on the FeDeriCa trial, a randomized, open-label, multicenter comparability study of pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection compared with intravenous pertuzumab and intravenous trastuzumab administered in the neoadjuvant and adjuvant settings with chemotherapy for the treatment of patients with early breast cancer. The pharmacokinetic endpoints were, first, to demonstrate that the exposure of subcutaneous pertuzumab was not inferior to that of intravenous pertuzumab, and then to demonstrate that the exposure of subcutaneous trastuzumab was not inferior to that of intravenous trastuzumab. The primary endpoints were met with the observed lower limit of the two-sided 90% confidence intervals above the prespecified noninferiority margins. The most common adverse reactions were alopecia, nausea, diarrhea, anemia, and asthenia. The totality of the evidence demonstrated comparability of the subcutaneous product to intravenous, allowing for extrapolation and approval of all breast cancer indications for which intravenous trastuzumab and pertuzumab are approved.